Regulation of cell functions by deubiquitinating enzymes

• Project/Area Number: 22370068
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cell biology
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: KOMADA Masayuki 東京工業大学, 大学院・生命理工学研究科, 准教授 (10225568)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000); Fiscal Year 2012: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2011: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2010: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
• Keywords: タンパク質分解 / 細胞 / タンパク質 / 酵素 / 細胞生物学 / タンパク質品質管理 / 変性タンパク質 / アグリソーム / ユビキチン / 脱ユビキチン化酵素 / プロテアソーム / 核小体 / リボソーム生合成

Research Abstract

1) Deubiquitinating enzyme USP18 was implicated in the protection of cells from the toxicity of non-native defective proteins by sequestering them to the aggresome in human cells.2) Small molecules that bind to the nucleolar localization signal of deubiquitinating enzyme USP36 were identified and were shown to inhibit the nucleolar localization as well as the function of USP36 in human cells. 3) The ubiquitin-interacting motifs (UIMs) in USP37 were shown to play a role in increasing the isopeptidase activity of USP37 toward ubiquitin chains by binding to the ubiquitin chains and stably positioning them in close proximity to the catalytic core of USP37.

Research Products

• [Journal Article] ERK-dependent down-of UIM-bearing proteins regulates EGF receptor endocytosis from the plasma membrane (2013)
  • Author(s): Li, X, Mr. Bian, Y., Takizawa, Y., Hashimoto, T., Ikoma, T., Dr. Tanaka, J., Kitamura, N., Inagaki, Y., Komada, M., and Tanaka, T
  • Journal Title: Mol. Biol.Cell Volume: 23 Pages: 1343-1353
  • Peer Reviewed
• [Journal Article] In vivo assembly of the axon initial segment in motor neurons (2013)
  • Author(s): Le Bras, B., Freal, A., Czarnecki, A., Legendre, P., Bullier, E., Komada, M., Brophy, P.J., Davenne, M., and Couraud, F
  • Journal Title: Brain Struct. Funct Volume: 未定 Issue: 4 Pages: 1433-1450
  • DOI: 10.1007/s00429-013-0578-7
  • Peer Reviewed
• [Journal Article] The ubiquitin code and its decoding machinery in the endocytic pathway (2013)
  • Author(s): Tanno, H. and Komada, M.
  • Journal Title: J. Biochem Volume: 153 Pages: 497-504
  • NAID: 40019655629
  • Peer Reviewed
• [Journal Article] Involvement of Src in the membrane skeletal complex, MPP6-4.1G, in Schmidt-Lanterman incisures of mouse myelinated nerve fibers in PNS (2013)
  • Author(s): Terada, N., Saitoh, Y., Ohno, N., Komada, M., Yamauchi, J., and Ohno, S.
  • Journal Title: Histochem. Cell Biol Volume: 139 Issue: 2 Pages: 213-222
  • DOI: 10.1007/s00418-012-1073-6
  • Peer Reviewed
• [Journal Article] ユビキチン化によるFrizzledのリソソーム 分解を介した Wnt シグナル強度の制御 (2013)
  • Author(s): Daocharad Burana、後藤聡、駒田雅之
  • Journal Title: 細胞工学 特集「Wnt協奏曲」 Volume: 32 Pages: 396-400
• [Journal Article] The ubiquitin code and its decoding machinery in the endocytic pathway. (2013)
  • Author(s): Tanno, H.
  • Journal Title: J. Biochem. Volume: 153 Issue: 6 Pages: 497-504
  • DOI: 10.1093/jb/mvt028
  • Peer Reviewed
• [Journal Article] ユビキチン化によるFrizzledのリソソーム分解を介したWntシグナル強度の制御 (2013)
  • Author(s): Burana, D.
  • Journal Title: 細胞工学 Volume: 32 Pages: 396-400
• [Journal Article] Balanced ubiquitination determines cellular responsiveness to extracellular stimuli (2012)
  • Author(s): Mukai, A., Yamamoto-Hino, M., Komada, M., Okano, H., and Goto, S.
  • Journal Title: Cell. Mol. Life Sci. Volume: 69 Pages: 4007-4016
  • Peer Reviewed
• [Journal Article] The Ankrd 13 family of UIM-bearing proteins regulates EGF receptor endocytosis from the plasma membrane (2012)
  • Author(s): Tanno, H., Yamaguchi, T., Goto, E., Ishido, S., and Komada, M.
  • Journal Title: Mol. Biol. Cell Volume: 23 Pages: 1343-1353
  • Peer Reviewed
• [Journal Article] Essential function of protein 4.1G in targeting of MPP6 into Schmidt-Lanterman incisures in myelinated nerves (2012)
  • Author(s): Terada, N., Saitoh, Y., Ohno, N., Komada, M., Saitoh, S., Peles, E., and Ohno, S.
  • Journal Title: Mol. Cell. Biol Volume: 32 Pages: 199-205
  • Peer Reviewed
• [Journal Article] The Ankrd 13 family of UIM-bearing proteins regulates EGF receptor endocytosis from the plasma membrane (2012)
  • Author(s): Tanno, H.
  • Journal Title: Mol.Biol.Cell Volume: 23 Issue: 7 Pages: 1343-1353
  • DOI: 10.1091/mbc.e11-09-0817
  • Peer Reviewed
• [Journal Article] Balanced ubiquitination determines cellular responsiveness to extracellular stimuli. (2012)
  • Author(s): Mukai, A.
  • Journal Title: Cell. Mol. Life Sci. Volume: 69 Issue: 23 Pages: 4007-4016
  • DOI: 10.1007/s00018-012-1084-4
  • Peer Reviewed
• [Journal Article] Essential fnction of protein 4.1G in targeting of membrane protein palmitoylated 6 into Schmidt-Lanterman incisures in myelinated nerves (2012)
  • Author(s): Terada N, et.al
  • Journal Title: Mol Cell Biol. Volume: 32 Issue: 1 Pages: 199-205
  • DOI: 10.1128/mcb.05945-11
  • Peer Reviewed
• [Journal Article] Nrk, an X-linked protein kinase in the germinal center kinase family, is required for placental development and fetoplacental induction of labor (2011)
  • Author(s): Denda, K., Nakao-Wakabayashi, K., Okamoto, N., Kitamura, N., Ryu, J.-Y., Tagawa, Y., Ichisaka, T., Yamanaka, S., and Komada, M
  • Journal Title: J. Biol. Chem Volume: 286 Pages: 28802-28810
  • Peer Reviewed
• [Journal Article] Leucine-rich repeat kinase LRRK1 regulates endosomal trafficking of the EGF regulation of Skp2 reduces Myc activity with receptor (2011)
  • Author(s): Hanafusa, H., Ishikawa, K., Kedashiro, S., Saigo, T., Iemura, S., Natsume, T., Komada, M., Shibuya, H., Nara, A., and Matsumoto, K
  • Journal Title: Nature Commun. 2 Volume: 158
  • Peer Reviewed
• [Journal Article] ユビキチン化による核小体の構造と機能の制御 (2011)
  • Author(s): 駒田雅之
  • Journal Title: 生体の科学特集「細胞核-構造と機能」 Volume: 62 Pages: 422-423
• [Journal Article] Nrk, an X-linked protein kinase in the germinal center kinase family, is required for placental development and fetoplacental induction of labor (2011)
  • Author(s): Denda, K., et al
  • Journal Title: Journal of biological chemistry Volume: 286 Issue: 33 Pages: 28802-28810
  • DOI: 10.1074/jbc.m111.258160
  • Peer Reviewed
• [Journal Article] ユビキチン化による核小体の構造と機能の制御 (2011)
  • Author(s): 駒田雅之
  • Journal Title: 生体の科学 Volume: 62 Pages: 422-423
• [Journal Article] Leucine-rich repeat kinase LRRK1 regulates endosomal trafficking of the EGF receptor (2011)
  • Author(s): Hanafusa, H.
  • Journal Title: Nature Commun. Volume: 2 Pages: 158-158
  • Peer Reviewed
• [Journal Article] Balanced ubiquitylation and deubiquitylation of Frizzled regulate cellular responsiveness to Wg/Wnt (2010)
  • Author(s): Mukai, A., Yamamoto-Hino, M., Awano, W., Watanabe, W., Komada, M., and Goto, S.
  • Journal Title: EMBO J. Volume: 29 Pages: 2114-2125
  • Peer Reviewed
• [Journal Article] Dominant-negative mutations in α-II spectrin cause West syndrome with severe cerebral hypomyelination, spastic quadriplegia, and developmental delay (2010)
  • Author(s): Saitsu, H., Tohyama, J., Kumada, T., Egawa, K., Hamada, K., Okada, I., Mizuguchi, T., Osaka, H., Miyata, R., Furukawa, T., Haginoya, K., Hoshino, H., Goto, T., Hachiya, Y., Yamagata, T., Saitoh, S., Nagai, T., Nishiyama, K., Nishimura, A., Miyake, N., Komada, M., Hayashi, K., Hirai, S., Ogata, K., Kato, M., Fukuda, A., and Matsumoto, N.
  • Journal Title: Am. J. Hum. Genet Volume: 86 Pages: 881-891
  • Peer Reviewed
• [Journal Article] Activated microglia mediate axo-glial disruption that contributes to axonal injury in multiple sclerosis (2010)
  • Author(s): Howell, O.W., Rundle, J.L., Garg, A., Komada, M., Brophy, P.J., and Reynolds, R.
  • Journal Title: J. Neuropathol. Exp. Neurol. Volume: 69 Pages: 1017-1033
  • Peer Reviewed
• [Journal Article] Involvement of a membrane skeletal protein, 4.1G, for Sertoli/germ cell interaction. (2010)
  • Author(s): Terada, N., Ohno, N., Saitoh, S., Saitoh, Y., Komada, M., Kubota, H., and Ohno, S.
  • Journal Title: Reproduction Volume: 139 Pages: 883-892
  • Peer Reviewed
• [Journal Article] 受容体のユビキチン化と脱ユビキチン化を介した細胞のWnt応答性の制御 (2010)
  • Author(s): 駒田雅之、後藤聡
  • Journal Title: 細胞工学特集「拡大するユビキチンバイオロジー」 Volume: 29 Pages: 1237-1243
• [Journal Article] 脱ユビキチン化酵素群の細胞機能 (2010)
  • Author(s): 駒田雅之、遠藤彬則
  • Journal Title: 生化学 Volume: 82 Pages: 378-387
  • NAID: 10026425815
  • Peer Reviewed
• [Journal Article] 軸索に特異的なスペクトリン細胞膜骨格の機能 (2010)
  • Author(s): 駒田雅之
  • Journal Title: 生体の科学特集「シナプスをめぐるシグナリング」 Volume: 61 Pages: 498-499
• [Journal Article] Dominant-negative mutations in α-II spectrin cause West syndrome with severe cerebral hypomyelination, spastic quadriplegia, and developmental delay (2010)
  • Author(s): Saitsu, H.
  • Journal Title: Am.J.Hum.Genet. Volume: 86 Pages: 881-891
  • Peer Reviewed
• [Journal Article] Activated microglia mediate axo-glial disruption that contributes to axonal injury in multiple sclerosis (2010)
  • Author(s): Howell, O.W.
  • Journal Title: J.Neuropathol.Exp.Neurol. Volume: 69 Pages: 1017-1033
  • Peer Reviewed
• [Journal Article] Involvement of a membrane skeletal protein, 4.1G, for Sertoli/germ cell interaction (2010)
  • Author(s): Terada, N.
  • Journal Title: Reproduction Volume: 139 Pages: 883-892
  • Peer Reviewed
• [Journal Article] 受容体のユビキチン化と脱ユビキチン化を介した細胞のWnt応答性の制御 (2010)
  • Author(s): 駒田雅之
  • Journal Title: 細胞工学 Volume: 29 Pages: 1237-1243
• [Journal Article] 軸索に特異的なスペクトリン細胞膜骨格の機能 (2010)
  • Author(s): 駒田雅之
  • Journal Title: 生体の科学 Volume: 61 Pages: 498-499
• [Presentation] Rolesof the Ankrd 13 familyofubiquitin-bindingproteinsintheendocyticpathway (2013)
  • Author(s): 駒田雅之
  • Organizer: 日本生化学会大会・インターナショナルセッション・リソソーム生物学のフロンティア
  • Place of Presentation: パシフィコ横浜、横浜
  • Year and Date: 2013-09-11
• [Presentation] ユビキチン化と脱ユビキチン化によるストレス顆粒の制御 (2013)
  • Author(s): 駒田雅之
  • Organizer: 日本細胞生物学会大会・シンポジウム-タンパク質分解システムによる細胞制御
  • Place of Presentation: ウイング愛知、名古屋
  • Year and Date: 2013-06-21
• [Presentation] タイトル未定 (2013)
  • Author(s): 駒田雅之
  • Organizer: 日本分子生物学会大会・ワークショップ-ER・Post-ERにおける膜プロテオスタシスネットワーク研究の新展開
  • Place of Presentation: 神戸国際会議場、神戸
• [Presentation] ユビキチン化と脱ユビキチン化によるストレス顆粒の制御 (2013)
  • Author(s): 駒田 雅之
  • Organizer: 第65回日本細胞生物学会
  • Place of Presentation: ウインク愛知（愛知県）
  • Invited
• [Presentation] Recognition of K63-linked ubiquitin chains by the Ankrd13 family of UIM-bearing proteins regulates endocytosis of plasma membrane proteins. (2013)
  • Author(s): 駒田 雅之
  • Organizer: 第35回内藤コンファレンス
  • Place of Presentation: シャトレーゼ ガトーキングダム サッポロ（北海道）
• [Presentation] タイトル未定 (2013)
  • Author(s): 駒田 雅之
  • Organizer: 第86回日本生化学会
  • Place of Presentation: パシフィコ横浜（神奈川県）
  • Invited
• [Presentation] タイトル未定 (2013)
  • Author(s): 駒田 雅之
  • Organizer: 第36回日本分子生物学会
  • Place of Presentation: 神戸国際会議場（兵庫県）
  • Invited
• [Presentation] 脱ユビキチン化酵素による細胞のストレス応答の制御 (2012)
  • Author(s): 駒田雅之
  • Organizer: 日本生化学会大会・シンポジウム-ベールを脱いだユビキチン系の新機能
  • Place of Presentation: 福岡国際会議場、福岡
  • Year and Date: 2012-12-16
• [Presentation] The Ankrd 13 family of UIM-bearing proteins regulates endocytosis of ubiquitinated cell surface proteins. (2012)
  • Author(s): 丹野 秀崇
  • Organizer: 第64回日本細胞生物学会
  • Place of Presentation: 神戸国際会議場（兵庫県）
• [Presentation] A deubiquitinating enzyme family protein USP18 is implicated in elimination of misfiled proteins by the proteasome. (2012)
  • Author(s): 小林 倫之
  • Organizer: 第64回日本細胞生物学会
  • Place of Presentation: 神戸国際会議場（兵庫県）
• [Presentation] 脱ユビキチン化酵素による細胞のストレス応答の制御 (2012)
  • Author(s): 駒田 雅之
  • Organizer: 第85回日本生化学会
  • Place of Presentation: 福岡国際会議場（福岡県）
  • Invited
• [Presentation] 脱ユビキチン化酵素USP13によるストレス顆粒の制御 (2012)
  • Author(s): 松本 俊介
  • Organizer: 第85回日本生化学会
  • Place of Presentation: 福岡国際会議場（福岡県）
• [Presentation] 脱ユビキチン化酵素USP18はユビキチン化された変性タンパク質によるアグリソーム形成に関与する (2012)
  • Author(s): Bolotbyek Avliush
  • Organizer: 第85回日本生化学会
  • Place of Presentation: 福岡国際会議場（福岡県）
• [Presentation] 肝細胞増殖因子HGFによる細胞内シグナルの連続した活性化は肝細胞株HepG2の不可逆的な増殖停止を誘導する (2011)
  • Author(s): 瀧澤友里
  • Organizer: 第34回日本分子生物学会
  • Place of Presentation: パシフィコ横浜(横浜)
  • Year and Date: 2011-12-16
• [Presentation] Involvement of ERK-dependent SKP2 down-regulation in HGF-induced inhibition of HepG2 hepatoma cell proliferation (2011)
  • Author(s): Li, X.
  • Organizer: 第34回日本分子生物学会
  • Place of Presentation: パシフィコ横浜(横浜)
  • Year and Date: 2011-12-16
• [Presentation] 新規CdkインヒビターInk4Xのツメガエル初期胚頭部形成における役割 (2011)
  • Author(s): 仁禮綾香
  • Organizer: 第34回日本分子生物学会
  • Place of Presentation: パシフィコ横浜(横浜)
  • Year and Date: 2011-12-13
• [Presentation] 新規ユビキチン結合因子Ankrd13によるエンドサイトーシス制御 (2011)
  • Author(s): 丹野秀崇、山口鉄平、後藤栄治、石戸聡、駒田雅之
  • Organizer: 日本生化学会大会・シンポジウム-拡大するユビキチンバイオロジー
  • Place of Presentation: 国立京都国際会館、京都
  • Year and Date: 2011-09-23
• [Presentation] 新規ユビキチン結合因子Ankrd13によるエンドサイトーシス制御 (2011)
  • Author(s): 駒田雅之
  • Organizer: 第84回日本生化学会
  • Place of Presentation: 京都国際会館(京都)(招待講演)
  • Year and Date: 2011-09-23
• [Presentation] 新規ユビキチン結合タンパク質ファミリーANKRD13のEGF受容体ダウンレギュレーションにおける機能 (2011)
  • Author(s): 丹野秀崇
  • Organizer: 第84回日本生化学会
  • Place of Presentation: 京都国際会館(京都)
  • Year and Date: 2011-09-23
• [Presentation] Regulation of the deubiquitinating enzyme USP36 during mitosis (2010)
  • Author(s): 遠藤彬則
  • Organizer: 第33回日本分子生物学会/第83回日本生化学学会合同大会BMB2010
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-10
• [Presentation] Nrk is a Ser/Thr kinase required for placental development and labor induction (2010)
  • Author(s): 伝田公紀
  • Organizer: 第33回日本分子生物学会/第83回日本生化学学会合同大会BMB2010
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-10
• [Presentation] ANKRD13 family of ubiquitin-binding proteins are possibly involved in endocytosis of epidermal growth factor receptor (2010)
  • Author(s): 丹野秀崇
  • Organizer: 第33回日本分子生物学会/第83回日本生化学学会合同大会BMB2010
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-08
• [Presentation] USP36, a nucleolar deubiquitinating enzyme (2010)
  • Author(s): Endo, A.
  • Organizer: 第33回日本分子生物学会/第83回日本生化学学会合同大会BMB2010
  • Place of Presentation: Cambridge, UK
  • Year and Date: 2010-07-20
• [Book] 生化学事典 (2011)
  • Author(s): 駒田雅之
  • Publisher: 「エンドサイトーシス」「FYVEドメイン」
• [Remarks] 東京工業大学 大学院生命理工学研究科 駒田研究室
  • URL: http://www.komada-lab.bio.titech.ac.jp
• [Remarks]
  • URL: http://www.kitamura-komada-lab.bio.titech.ac.jp
• [Remarks]
  • URL: http://www.kitamura-komada-lab.bio.titech.ac.jp